Dataset of mitochondrial genome variants associated with asymptomatic atherosclerosis.

This dataset report is dedicated to mitochondrial genome variants associated with asymptomatic atherosclerosis. These data were obtained using the method of next generation pyrosequencing (NGPS). The whole mitochondrial genome of the sample of patients from the Moscow region was analyzed. In this article the dataset including anthropometric, biochemical and clinical parameters along with detected mtDNA variants in patients with carotid atherosclerosis and healthy individuals was presented. Among 58 of the most common homoplasmic mtDNA variants found in the observed sample, 7 variants occurred more often in patients with atherosclerosis and 16 variants occurred more often in healthy individuals.

Mitochondrial genome sequencing in atherosclerosis: what's next?

Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease.

Association of mitochondrial mutations with the age of patients having atherosclerotic lesions.

Mitochondrial genome mutations are associated with different pathologies. Earlier the authors of the study found an association of some mitochondrial genome mutations with atherosclerosis. In the present study, an attempt to analyze a connection of detected mutations with the age of patients with atherosclerosis was made. The investigated sample included 700 individuals, examined by ultrasonography in polyclinics of Moscow and the Moscow region. The sample was divided approximately into two equal parts. The first part included patients with carotid atherosclerosis. The second part included conventionally healthy study participants. In PCR-fragments of individuals' DNA the heteroplasmy level of investigated mutations was quantitatively measured by the method, developed by members of our laboratory on the basis of pyrosequencing technology. According to the obtained results mutations G12315A, G14459A and G15059A were significantly associated with the age of the study participants. The same time one nucleotide replacements A1555G and G14846A correlated negatively with the age at a high level of significance. Thus, in the present study an association of atherogenic mitochondrial genome mutations with age was found. Antiatherogenic mutations were correlated with the age negatively. This prompts a suggestion about common mechanisms of atherogenesis and aging.

Mutations of mitochondrial genome in carotid atherosclerosis.

With aim of detection the spectrum of mitochondrial DNA mutations in patients with carotid atherosclerosis from Moscow Region, we used a Roche 454 high-throughput sequencing of the whole mitochondrial genome. We have found that the presence of a number of homoplasmic mitochondrial DNA mutations in genes of 16S ribosomal RNA, subunits 2, 4, and 5 NADH dehydrogenase, subunits 1 and 2 cytochrome C oxidase, subunit 6 ATP-synthase, tRNA- Leu 2 and cytochrome B differed between conventionally healthy participants of the study and patients with carotid atherosclerosis. We also found heteroplasmic mutations, including insertions one or several nucleotides, that occurred more frequently in mitochondrial DNA of conventionally healthy participants of the study or patients with atherosclerotic lesions.

Mosaicism of mitochondrial genetic variation in atherosclerotic lesions of the human aorta.

OBJECTIVE: The aim of the present study was an analysis of heteroplasmy level in mitochondrial mutations 652delG, A1555G, C3256T, T3336C, 652insG, C5178A, G12315A, G13513A, G14459A, G14846A, and G15059A in normal and affected by atherosclerosis segments of morphologically mapped aortic walls. METHODS: We investigated the 265 normal and atherosclerotic tissue sections of 5 human aortas. Intima of every aorta was divided according to morphological characteristics into segments with different types of atherosclerotic lesions: fibrous plaque, lipofibrous plaque, primary atherosclerotic lesion (fatty streak and fatty infiltration), and normal intima from human aorta. PCR-fragments were analyzed by a new original method developed in our laboratory on the basis of pyrosequence technology. RESULTS: According to the obtained data, mutations G12315A and G14459A are significantly associated with total and primary atherosclerotic lesions of intimal segments and lipofibrous plaques (P ≤ 0.01 and P ≤ 0.05, accordingly). Mutation C5178A is significantly associated with fibrous plaques and total atherosclerotic lesions (P ≤ 0.01). A1555G mutation shows an antiatherosclerotic effect in primary lesion in lipofibrous plaques (P ≤ 0.05). Meanwhile, G14846A mutation is antiatherogenic for lipofibrous plaques (P ≤ 0.05). CONCLUSION: Therefore, mutations C5178A, G14459A, G12315A, A1555G, and G14846A were found to be associated with atherosclerotic lesions.